{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Moulding DA"],"funding":["Great Ormond Street Hospital Childrens Charity","National Institute for Health Research (NIHR)","Wellcome Trust"],"pagination":["3803-11"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4338607"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["120(18)"],"pubmed_abstract":["The constitutively active mutant of the Wiskott-Aldrich Syndrome protein (CA-WASp) is the cause of X-linked neutropenia and is linked with genomic instability and myelodysplasia. CA-WASp generates abnormally high levels of cytoplasmic F-actin through dysregulated activation of the Arp2/3 complex leading to defects in cell division. As WASp has no reported role in cell division, we hypothesized that alteration of cell mechanics because of increased F-actin may indirectly disrupt dynamic events during mitosis. Inhibition of the Arp2/3 complex revealed that excess cytoplasmic F-actin caused increased cellular viscosity, slowed all phases of mitosis, and perturbed mitotic mechanics. Comparison of chromosome velocity to the cytoplasmic viscosity revealed that cells compensated for increased vis"],"journal":["Blood"],"pubmed_title":["Excess F-actin mechanically impedes mitosis leading to cytokinesis failure in X-linked neutropenia by exceeding Aurora B kinase error correction capacity."],"pmcid":["PMC4338607"],"funding_grant_id":["092825","090233","V1259","V1223","NF-SI-0611-10001"],"pubmed_authors":["Thrasher AJ","Moeendarbary E","Moulding DA","Record J","Charras GT","Valon L"],"additional_accession":[]},"is_claimable":false,"name":"Excess F-actin mechanically impedes mitosis leading to cytokinesis failure in X-linked neutropenia by exceeding Aurora B kinase error correction capacity.","description":"The constitutively active mutant of the Wiskott-Aldrich Syndrome protein (CA-WASp) is the cause of X-linked neutropenia and is linked with genomic instability and myelodysplasia. CA-WASp generates abnormally high levels of cytoplasmic F-actin through dysregulated activation of the Arp2/3 complex leading to defects in cell division. As WASp has no reported role in cell division, we hypothesized that alteration of cell mechanics because of increased F-actin may indirectly disrupt dynamic events during mitosis. Inhibition of the Arp2/3 complex revealed that excess cytoplasmic F-actin caused increased cellular viscosity, slowed all phases of mitosis, and perturbed mitotic mechanics. Comparison of chromosome velocity to the cytoplasmic viscosity revealed that cells compensated for increased vis","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Nov","modification":"2025-06-25T03:03:54.139Z","creation":"2025-06-25T03:03:54.139Z"},"accession":"S-EPMC4338607","cross_references":{"pubmed":["22972986"],"doi":["10.1182/blood-2012-03-419663"]}}